Figure 1.

Analysis flowchart. First, the analysis of the cross-sectional association between the plasma amyloid-β (Aβ) peptides (Aβ₄₂, Aβ₄₀, and Aβ₄₂/Aβ₄₀ ratio) and circulating protein was conducted in a subset of the Atherosclerosis Risk in Communities (ARIC) participants with plasma Aβ data available (yellow box). Next, circulating proteins with significant association with the Aβ peptides were assessed for their association with incident dementia in the overall ARIC cohort at two separated baselines followed by replication in the Age, Gene/Environment Susceptibility–Reykjavik Study (AGES) (blue boxes). Finally, the variances of the plasma Aβ peptides were quantified, and the results of the cross-sectional association between plasma Aβ and circulating proteins were further characterized using gene set and tissue enrichment analysis (orange boxes).